嘧啶连接的苯并噻唑的抗惊厥潜力的硅内研究、设计和合成。

Amol Kale, Rajendra Kakde, Smita Pawar, Rutuja Thombare, Dhanashree Zope, Ishwar Kakde
{"title":"嘧啶连接的苯并噻唑的抗惊厥潜力的硅内研究、设计和合成。","authors":"Amol Kale, Rajendra Kakde, Smita Pawar, Rutuja Thombare, Dhanashree Zope, Ishwar Kakde","doi":"10.2174/0115701638299019240418055933","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The objective of the study was to design and synthesize a series of N-(6-substituted-1,3-benzothiazole- 2-yl)-2-{[6-(3-substitutedphenyl)-5-cyano-2-sulfanylpyrimidine-4-yl)]amino}acetamide derivatives BPD (1-15) that contains key pharmacophores required for anticonvulsant action.</p><p><strong>Methods: </strong>The titled compounds (BPD 1-15) were synthesized by reacting 2-substituted-N-(6-chlorobenzo[d]thiazol2-yl)acetamide with 4-amino-6-(4-substituted phenyl)-2-mercapto pyrimidine 5-carbonitrile in the presence of potassium carbonate and dry acetone. The synthesized compounds BPD (1-15) were assessed in vivo by the maximum electric shock (MES) test and the subcutaneous pentylenetetrazol (scPTZ) test in mice. The neurotoxicity test was performed by the rotarod test. A molecular docking study of title compounds with a sodium channel receptor (PDB ID: 1BYY) was carried out using the SP Docking protocol of the Glide module of the Maestro. Pharmacophore modeling was used to qualitatively identify the chemical characteristics for ligand binding and their spatial configurations in the 3D space of the active site.</p><p><strong>Result: </strong>Among the studied compounds, BPD-15 and BPD-5 compounds showed significant action in both the MES and scPTZ models, with no neurotoxicity. BPD-15 & BPD-5 were relatively safe in acute toxicity testing. Compounds BPD-15 and BPD-5 showed good dock scores of -6.434 and -6.191, respectively.</p><p><strong>Conclusion: </strong>Thus, the compounds BPD-15 and BPD-5 have shown a considerable affinity towards the sodium channel as compared to the standard drug Riluzole. Compound BPD-14 showed good drug compatibility, and compounds BPD-1, BPD-2, BPD-11, BPD-12, BPD-13, BPD-14, BPD-15 showed good ADME values.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In-silico Studies, Design, and Synthesis of Pyrimidine-linked Benzothiazoles for its Anticonvulsant Potential.\",\"authors\":\"Amol Kale, Rajendra Kakde, Smita Pawar, Rutuja Thombare, Dhanashree Zope, Ishwar Kakde\",\"doi\":\"10.2174/0115701638299019240418055933\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The objective of the study was to design and synthesize a series of N-(6-substituted-1,3-benzothiazole- 2-yl)-2-{[6-(3-substitutedphenyl)-5-cyano-2-sulfanylpyrimidine-4-yl)]amino}acetamide derivatives BPD (1-15) that contains key pharmacophores required for anticonvulsant action.</p><p><strong>Methods: </strong>The titled compounds (BPD 1-15) were synthesized by reacting 2-substituted-N-(6-chlorobenzo[d]thiazol2-yl)acetamide with 4-amino-6-(4-substituted phenyl)-2-mercapto pyrimidine 5-carbonitrile in the presence of potassium carbonate and dry acetone. The synthesized compounds BPD (1-15) were assessed in vivo by the maximum electric shock (MES) test and the subcutaneous pentylenetetrazol (scPTZ) test in mice. The neurotoxicity test was performed by the rotarod test. A molecular docking study of title compounds with a sodium channel receptor (PDB ID: 1BYY) was carried out using the SP Docking protocol of the Glide module of the Maestro. Pharmacophore modeling was used to qualitatively identify the chemical characteristics for ligand binding and their spatial configurations in the 3D space of the active site.</p><p><strong>Result: </strong>Among the studied compounds, BPD-15 and BPD-5 compounds showed significant action in both the MES and scPTZ models, with no neurotoxicity. BPD-15 & BPD-5 were relatively safe in acute toxicity testing. Compounds BPD-15 and BPD-5 showed good dock scores of -6.434 and -6.191, respectively.</p><p><strong>Conclusion: </strong>Thus, the compounds BPD-15 and BPD-5 have shown a considerable affinity towards the sodium channel as compared to the standard drug Riluzole. Compound BPD-14 showed good drug compatibility, and compounds BPD-1, BPD-2, BPD-11, BPD-12, BPD-13, BPD-14, BPD-15 showed good ADME values.</p>\",\"PeriodicalId\":93962,\"journal\":{\"name\":\"Current drug discovery technologies\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current drug discovery technologies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0115701638299019240418055933\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug discovery technologies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115701638299019240418055933","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

背景:本研究的目的是设计和合成一系列 N-(6-取代-1,3-苯并噻唑-2-基)-2-{[6-(3-取代苯基)-5-氰基-2-硫基嘧啶-4-基)]氨基}乙酰胺衍生物 BPD (1-15),该衍生物含有抗惊厥作用所需的关键药效团:方法:在碳酸钾和干丙酮存在下,通过 2-取代-N-(6-氯苯并[d]噻唑2-基)乙酰胺与 4-氨基-6-(4-取代苯基)-2-巯基嘧啶 5-甲腈反应合成了标题化合物(BPD 1-15)。通过对小鼠进行最大电击(MES)试验和皮下注射戊四唑(scPTZ)试验,对合成的化合物 BPD(1-15)进行了体内评估。神经毒性试验是通过旋转体试验进行的。利用 Maestro 的 Glide 模块中的 SP Docking 协议,对标题化合物与钠通道受体(PDB ID:1BYY)进行了分子对接研究。药理模型用于定性鉴定配体结合的化学特征及其在活性位点三维空间中的空间构型:结果:在所研究的化合物中,BPD-15 和 BPD-5 化合物在 MES 和 scPTZ 模型中均表现出显著作用,且无神经毒性。BPD-15 和 BPD-5 在急性毒性测试中相对安全。BPD-15和BPD-5化合物显示出良好的对接得分,分别为-6.434和-6.191:因此,与标准药物利鲁唑相比,化合物 BPD-15 和 BPD-5 对钠通道具有相当大的亲和力。化合物 BPD-14 显示出良好的药物相容性,化合物 BPD-1、BPD-2、BPD-11、BPD-12、BPD-13、BPD-14 和 BPD-15 显示出良好的 ADME 值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In-silico Studies, Design, and Synthesis of Pyrimidine-linked Benzothiazoles for its Anticonvulsant Potential.

Background: The objective of the study was to design and synthesize a series of N-(6-substituted-1,3-benzothiazole- 2-yl)-2-{[6-(3-substitutedphenyl)-5-cyano-2-sulfanylpyrimidine-4-yl)]amino}acetamide derivatives BPD (1-15) that contains key pharmacophores required for anticonvulsant action.

Methods: The titled compounds (BPD 1-15) were synthesized by reacting 2-substituted-N-(6-chlorobenzo[d]thiazol2-yl)acetamide with 4-amino-6-(4-substituted phenyl)-2-mercapto pyrimidine 5-carbonitrile in the presence of potassium carbonate and dry acetone. The synthesized compounds BPD (1-15) were assessed in vivo by the maximum electric shock (MES) test and the subcutaneous pentylenetetrazol (scPTZ) test in mice. The neurotoxicity test was performed by the rotarod test. A molecular docking study of title compounds with a sodium channel receptor (PDB ID: 1BYY) was carried out using the SP Docking protocol of the Glide module of the Maestro. Pharmacophore modeling was used to qualitatively identify the chemical characteristics for ligand binding and their spatial configurations in the 3D space of the active site.

Result: Among the studied compounds, BPD-15 and BPD-5 compounds showed significant action in both the MES and scPTZ models, with no neurotoxicity. BPD-15 & BPD-5 were relatively safe in acute toxicity testing. Compounds BPD-15 and BPD-5 showed good dock scores of -6.434 and -6.191, respectively.

Conclusion: Thus, the compounds BPD-15 and BPD-5 have shown a considerable affinity towards the sodium channel as compared to the standard drug Riluzole. Compound BPD-14 showed good drug compatibility, and compounds BPD-1, BPD-2, BPD-11, BPD-12, BPD-13, BPD-14, BPD-15 showed good ADME values.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信